Role of mitochondrial DNA variants in the development of fragile X-associated tremor/ataxia syndrome.
Ataxia
/ genetics
DNA, Mitochondrial
/ genetics
Fragile X Mental Retardation Protein
/ genetics
Fragile X Syndrome
/ genetics
Gene Frequency
Genetic Association Studies
Genetic Variation
Heteroplasmy
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mitochondria
/ genetics
Tremor
/ genetics
Whole Genome Sequencing
/ methods
FMR1 premutation
FXTAS
Low-level heteroplasmic variants
Mitogenome
Risk factors
mtDNA haplogroups
Journal
Mitochondrion
ISSN: 1872-8278
Titre abrégé: Mitochondrion
Pays: Netherlands
ID NLM: 100968751
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
12
07
2019
revised:
08
01
2020
accepted:
09
03
2020
pubmed:
17
3
2020
medline:
8
6
2021
entrez:
17
3
2020
Statut:
ppublish
Résumé
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that appears in at least one-third of adult carriers of FMR1 premutation. Several studies have shown that mitochondrial dysfunction may play a role in neurodegenerative disorders. In order to assess whether mitochondrial DNA variants are involved in the risk of developing FXTAS we evaluated the frequency of mitochondrial haplogroups in 132 unrelated Spanish FMR1 premutation carriers. In addition, the entire mitogenome of 26 FMR1 premutation carriers was sequenced using massively parallel sequencing technologies to analyze mitochondrial DNA variants. Statistical analyses reveal a significant difference in the frequency of T haplogroup. Data analysis of mitochondrial DNA sequences evidence an association between FXTAS and the burden of heteroplasmic variants as well as their distribution. Our results suggest that haplogroup T might be a potential protective factor for FXTAS and that FXTAS individuals accumulate higher rates of heteroplasmic variants in compromised regions of the mitochondrial genome. These results may explain, in part, the role of mitochondrial DNA in the development of FXTAS.
Identifiants
pubmed: 32173566
pii: S1567-7249(19)30185-0
doi: 10.1016/j.mito.2020.03.004
pii:
doi:
Substances chimiques
DNA, Mitochondrial
0
FMR1 protein, human
0
Fragile X Mental Retardation Protein
139135-51-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
157-162Informations de copyright
Copyright © 2020. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.